A better understanding of the dynamic physical and biomolecular cues present in tissue microenvironments has led to a growing interest in the development of biomaterial systems for improved 3D culture environments, as well as delivery vehicles for cell-based therapies. As discovery of new biological signals and targets has evolved, so has the need for improved delivery systems to facilitate improvements in wound healing, stem cell engraftment, and reversal of fibrotic diseases. As a result, biomaterial scaffolds based on both protein components and highly tunable synthetic chemistries have evolved to address many of these needs. This talk will highlight several examples in which advances in four-dimensional control of scaffold properties can be used to better understand how to present and manipulate the presentation of biochemical signals, as well as to promote tissue regeneration.